Introduction cGMP regulations Subparts of 21 CFR part 11 Duties of QC unit under cGMP regulations Quality assurance function Question References

1. Topic:- Role of quality systems & audits in
pharmaceutical manufacturing environment: cGMP
regulations & quality assurance functions
Subject Name :- Audits & Regulatory Compliance
Subject Code:- MQA20T
Department of Pharmaceutical Quality Assurance
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav–vapi
Presented by:-
Machhi Dhruvi A.
2nd sem M.Pharm.
Guided by:-
Dr. D. P. Damahe
Associate Professor

2. CONTENTS
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1. Introduction
2. cGMP regulations
3. Subparts of 21 CFR part 11
4. Duties of QC unit under cGMP regulations
5. Quality assurance function
6. Question
7. References

3. 1. INTRODUCTION
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• By regulation, appropriate practice & common sense, quality assurance (QA) is a
critical function in the pharmaceutical manufacturing environment.
• The need for an independent unit to audit & comment on the appropriate application
of standard operating procedures, master batch records, procedures approved in
product applications & the proper functioning of the quality control (QC) unit is
paramount.
• This helps assure that products are manufactured reliably, with adherence to approved
specifications & that current good manufacturing practices (cGMP) are maintained in
conformance to regulation, both in the facility in general & the microenvironment of
each product’s manufacturing sequence.

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• The cGMP regulations establish requirements that are intended to provide a high level
of assurance that the pharmaceutical products produced satisfy the strength, purity,
potency & other quality requirements established for the finished product to assure
that it is fit for its intended use.
• Manufacturers must establish a quality control (QC) unit that is responsible for many
of the quality-related activities required by the regulations.
• Pharmaceutical product manufacturers are increasingly interested in implementing a
comprehensive quality management system (QMS) & employing risk management
approaches because they allow them to apply newer quality management principles
that they believe enable them to more effectively assure product quality & better allow
harmonization with evolving international regulatory quality system requirements.

5. 2. cGMP REGULATIONS
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• The cGMP regulations for the manufacture of pharmaceutical products are contained
in Parts 210 & 211 of Title 21 of the Code of Federal Regulations (CFR).
• Part 210 specifies the scope & applicability of the cGMP regulations & defines terms
used in the regulations.
• It also indicates that the regulations establish “ minimum ” cGMP requirements & that
products that are not manufactured under cGMP are adulterated. Adulterated products
& the persons responsible for the adulteration are subject to regulatory action by the
FDA.
• Part 211 contains specific GMP requirements for finished pharmaceuticals.

6. 3. SUBPARTS OF 21 CFR PART 11
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• Part 211 contains specific good manufacturing practice (GMP) requirements for
finished pharmaceuticals & is divided into Subparts A – K as follows:
A. Scope
B. Organization & Personnel
C. Buildings & Facilities
D. Equipment
E. Control of Components & Drug Product Containers & Closures
F. Production & Process Controls
G. Packaging & Labeling Control
H. Holding & Distribution
I. Laboratory Controls
J. Records & Reports
K. Returned & Salvaged Drug Products

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• The cGMP regulations are written to address the primary potential sources of product
variability.
Subpart B
• establishes the quality control (QC) unit & the duties of that unit,
• establishes personnel requirements &
• addresses personnel practices (e.g. sanitation) intended to reduce the likelihood of
product contamination.
Subparts C & D
• establish requirements for buildings & facilities & equipment used in the manufacture,
processing, packing, or holding of a drug product.

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Subparts E, F, G & H
• establish controls over the major processes associated with the production of a
finished & packaged drug product that is ready to be shipped for distribution to users.
• Controls are established for incoming raw materials & components & continue
through manufacturing, packaging, labeling, holding & distribution of finished,
packaged, labeled & released drug product.
Subpart I
• It requires the establishment of scientifically sound & appropriate specifications,
standards, sampling plans & test procedures;
• requires instrument specifications & calibration; &
• establishes lot or batch testing & release requirements.

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Subpart J
• establishes documentation requirements including master & batch records
Subpart K
• addresses the control & disposition of returned drug products & places limitations on
the salvage of drug products that have been subjected to improper storage conditions
(e.g., smoke, heat, fire, moisture).

10. 4. DUTIES OF QC UNIT UNDER cGMP REGULATIONS
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• The cGMP regulations assign specific duties to the quality control (QC) unit:
The unit is required to have the responsibility & authority to approve or reject all
components, drug product containers, closures, in-process materials, packaging
material labeling & drug products & the authority to review production records to
assure that no errors have occurred or, if errors have occurred, that they have been
fully investigated.
The responsibilities of the unit extend to approving or rejecting drug products
manufactured, processed, packed, or held by contract manufacturers.
The unit is also responsible for approving or rejecting all procedures or specifications
impacting on the identity, strength, quality & purity of the drug product.
• This includes review & approval of procedures for production & process control,
including any changes to these procedures.
• These procedures & the responsibilities & procedures applicable to the quality
control unit within the organization, must be written & followed.

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All specifications, standards, sampling plans, test procedures, or other laboratory
control mechanisms, including any changes, must be in writing & reviewed &
approved by the QC unit.
Written procedures describing the handling of all written & oral complaints regarding
a drug product are required.
The QC unit is responsible for reviewing any complaint involving the possible failure
of a drug product to meet any of its specifications & for such drug products, making a
determination as to the need for an investigation in accordance with cGMP
requirements.
• The review should include a determination if the complaint represents a serious &
unexpected adverse drug experience, which is required to be reported to the FDA.
• A written record of each complaint must be maintained in a complaint file.

12. 5. QUALITY ASSURANCE FUNCTION
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1. Ensuring proper warehousing practices:
• QA department is responsible for the proper storage of API & other excipients &
segregation of the material in the warehouse.
For Incoming components
API,
Excipients,
Packaging Materials,
containers & closures,
labels with proper storage conditions which is required for drug stability, etc.
2. Manufacturing process & critical process checks:
• This is one of the most critical activity performed by the QA department.
• For this Activity, special IPQA team (In Process Quality Assurance) is assigned which
keep a eye on all floor activities related to the storage of raw materials to the final
product dispatch.

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3. Process monitoring & Process controls:
• During the manufacturing of the product the whole process is monitored by the QA
department &
• ensuring that all the steps followed for the manufacturing of the product are validated
& as per SOP.
• If the any alteration in the method of manufacturing of the product is found, then the
appropriate action is taken by QA personnel to ensure the quality of the product.

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4. Batch Record Review:
• All the data which is generated during the manufacturing of the Pharmaceutical
product is recorded which tell us about the all essential data related to product
manufacturing, e.g.,
Timing of process
Ingredients
environmental conditions
person involve etc.
• QA person review the batch record to ensure the data enter in the batch record is
legible. If they found any kind of data integrity issues then the appropriate action is
taken as per the SOP.

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5. Final release of Drug Products for distribution & sale:
• When the Pharmaceutical product is manufactured & packed then the role of QA
comes to
ensure that the product is safe for market or not,
all the QC test reports are attached with batch record
all the calculation related to that batch are correct &
several other parameters are checked & after ensuring the product safety the QA
person allow to distribute the product in the market.

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6. Stability testing & evaluation of shelf-life of products:
• QA department is responsible for the stability testing of the pharmaceutical product
manufactured in their factory & ensure that the shelf life of the product is same as per
the study & mention on the product to avoid the market complains.
7. Ensuring proper warehousing of finished products:
• Storage condition plays an important role in the stability of the pharmaceutical
product, so the QA person ensures all the parameters which are required to prevent the
product decontamination during the storage.

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8. Complaints & product recalls:
• If any market complain come to the manufacturing factory, then it is a responsibility
of a QA department to act on that & to take appropriate action.
• If product recall is required from the market then the QA department initiate the recall
process & ensure all the products related to the complain batch is recalled.
9. Handling of Change Control Systems:
• Any other than validated step/ activity required to fix in any document & process is
taken through the change control system which is a documented process to apply
change in the Pharmaceutical industries.
• Change control system finally review by the QA department for approval.

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10. Out of specification investigations:
• In any case during the testing of any pharmaceutical product if the outcome is not as
per the expected outcome & the final result deviate from the standard specification
then the QA department should perform an investigation to find the root cause through
the specific SOP.
11. Returned products (salvage & disposal):
• When the product is returned in the manufacturing factory due to any reason then the
QA department is responsible to take action on the product.
• QA perform same addition process on the product to prevent or in case the product is
not salvage, the product is destroyed on the order of the QA department.

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12. Internal Quality Audits & Quality Review:
• Internal Audit is performed by QA department frequently (surprisingly or scheduled)
to ensure that all other department in the company is performing their activities as per
SOP.
• Quality Review is organized by the QA department to enhance the quality of the
output of the company in all aspects like
product quality
employee facility
infrastructure
machinery
company policies, etc.

20. 6. QUESTIONS
1. Discuss various duties of quality control unit under the cGMP regulation.[6]
2. What is cGMP? Describe general components of cGMP.[6]
3. Discuss functions of QA Department in Pharmaceutical Industry.[6]
4. Discuss quality assurance functions & quality system approaches in
pharmaceutical industries.[6]
5. Explain general cGMP regulation for pharmaceutical industries.[5] [2R]
6. Discuss quality assurance functions.[6]
7. Explain role of quality system & audits in pharmaceutical manufacturing [6]
8. Explain the audit role played by QA in quality control function.[6]
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21. 7. REFERENCES
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1. Siegel, E. B., & Barquest, J. M., Role of Quality Systems and Audits in
Pharmaceutical Manufacturing Environment. Pharmaceutical Manufacturing
Handbook: Regulations and Quality, 2008, pp 201-238.
2. Mrs. Janki Singh, “Quality Assurance Department Functions in
Pharmaceuticals”, October 2019, https://pharmabeginers.com/function-of-
quality-assurance-department-qa-in-pharmaceuticals/

22. Thank you
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